The etiology of juvenile-onset diabetes in the human is still unknown. The spontaneously diabetic Wistar rat develops a diabetic syndrome which bears several close resemblances to the human juvenile-onset diabetic. Like the human form, the disease has an early age of onset, a strong genetic component, occurs in lean animals and is characterized by hypoinsulinemia and ketosis, and pathologically by beta cell destruction and inflammatory cell infiltration. Thus, the spontaneously diabetic Wistar rat offers an attractive animal model for the study of the pathophysiology of juvenile-onset diabetes. The specific objectives of the present research proposal are: 1. To characterize the hormonal profile (growth homone, insulin, glucagon, and glucose) of young rats from the new breeding colony of the spontaneously diabetic Wistar rat (Bio Breeding Strain) under physiologic conditions, by use of a chronically catheterized model which allows frequent serial sampling of blood in freely-moving animals without disturbing their ongoing behavior. 2. To assess the possible role of somatostatin in diabetes by passive immunization with anti-somatostatin serum, infusion of somatostatin, and measurement of tissue levels of somatostatin. 3. To study the effects of dietary modifications, including a) dietary restriction, b) diets high in sucrose, and c) hyperphagia induced by neurosurgical procedures, on the course of development of the diabetic syndrome. 4. To modify the time of onset of the spontaneous diabetic state by treatment with immunosuppressive drugs (cyclophosphamide) and with sub-diabetogenic doses of streptozotocin.